title: MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma.
abstract: Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[-]) ALCLs, 9 angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(+) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b; 2 downregulated: miR-146a, miR-155) significantly associated with ALK(+) ALCL cases. In addition, we derived an 11-miRNA signature (4 upregulated: miR-210, miR-197, miR-191, miR-512-3p; 7 downregulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(-) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, the miR-17∼92 cluster and its paralogues were also highly expressed in ALK(+) ALCL and may represent important downstream effectors of the ALK oncogenic pathway.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE;
authors.forename: Cuiling
authors.initials: C
authors.lastname: Liu
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Yulei
authors.initials: Y
authors.lastname: Shen
authors.forename: Magdalena Julia
authors.initials: MJ
authors.lastname: Dabrowska
authors.forename: Karen
authors.initials: K
authors.lastname: Dybkaer
authors.forename: Megan S
authors.initials: MS
authors.lastname: Lim
authors.forename: Roberto
authors.initials: R
authors.lastname: Piva
authors.forename: Antonella
authors.initials: A
authors.lastname: Barreca
authors.forename: Elisa
authors.initials: E
authors.lastname: Pellegrino
authors.forename: Elisa
authors.initials: E
authors.lastname: Spaccarotella
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Lachel
authors.forename: Can
authors.initials: C
authors.lastname: Kucuk
authors.forename: Chun-Sun
authors.initials: CS
authors.lastname: Jiang
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Hu
authors.forename: Sharathkumar
authors.initials: S
authors.lastname: Bhagavathi
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Patricia
authors.initials: P
authors.lastname: Aoun
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
authors.forename: Timothy W
authors.initials: TW
authors.lastname: McKeithan
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000954:Antigens, Surface / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023061:Gene Order; D006801:Humans; D016130:Immunophenotyping; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D009928:Organ Specificity / Q000235:genetics; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D035683:MicroRNAs; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases